Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of a disease characterized by respiratory disorders in young pigs and reproductive failure in sows (Benfield et al., J. Vet. Diagn. Invest., 4:127-133 (1992); Collins et al., J. Vet. Diagn. Invest., 4:117-126 (1992); Wensvoort et al., Vet. Q., 13:121-130 (1991)) and is now endemic in most countries. The syndrome was first recognized as a “mystery swine disease” in the United States in 1987 and was discovered in Europe in 1990. The two prototype viral strains (Lelystad and VR-2332) differ in nucleotide sequence by approximately 40% and represent two distinct genotypes, referred to as European (EU or Type 1, Lelystad; Meulenberg et al., Virology, 192:62-72 (1993)) and North American (NA or Type 2, VR-2332; Nelsen et al., J. Virol., 73:270-80 (1999)) strains (Fang et al., Virus Res., 100:229-235 (2004); Mardassi et al., J. Gen. Virol., 75:681-5 (1994); Meng et al., Arch. Virol., 140:745-55 (1995); Ropp et al., J. Virol., 78:3684-3703 (2004)). The disease has also been referred to as Wabash syndrome, mystery pig disease, porcine reproductive and respiratory syndrome, swine plague, porcine epidemic abortion and respiratory syndrome, blue abortion disease, blue ear disease, abortus blau, and seuchenhafter spatabort der schweine. The disease is characterized by reproductive failure in pregnant sows and respiratory problems in pigs of all ages. The disease has a significant negative impact on the swine industry.
PRRSV is an enveloped, positive-sense RNA virus belonging to the family Arteriviridae in the order Nidovirales (Cavanagh, Arch. Virol., 142:629:633 (1997)). The PRRSV genome varies from 15.1-15.5 kb long (Meulenberg et al., Virology, 192:62-72 (1993); Nelsen et al., J. Virol., 73:270-80 (1999)). The first 75% of the genome encodes the replicase polyprotein essential for virus replication and is comprised of two large open reading frames (ORFs) (1a and 1b) that are processed cotranslationally into smaller proteins by virally encoded proteases (Snijder et al., J. Gen. Virol., 79:961-79 (1998)). The structural proteins are encoded by seven downstream ORFs and are translated from a 3′-coterminal nested set of subgenomic mRNAs (sgmRNA) (Meulenberg et al., Virology, 192:62-72 (1993); Pattnaik et al., Cell, 69:1011-1020 (1992)). In strain VR-2332, the coding region of the genome (15,411 bases) is flanked by 5′ and 3′ nontranslated regions of 189 and 151 nucleotides, respectively.
PRRSV strain VR-2332 has been well characterized in terms of its complete genome sequence (Pattnaik et al., Cell, 69:1011-1020 (1992)), the ability of PRRSV to constitutively produce defective subgenomic RNA species termed heteroclites (latin: uncommon forms) (Yuan et al., Virology, 275:158-169 (2000)); Yuan et al., Virus Research, 105:75-87 (2004)), and its growth properties in vitro as well as in vivo (Murtaugh et al., Vet. Immunol. Immunopathol., 102:105-349 (2004)). In addition, an infectious clone of this 15.4 kb NA PRRSV genome has been produced and examined for its ability to cause disease in swine (pVR-HN; Nielsen et al., J. Virol., 77:3702-3711 (2003)).
PRRSV continues to cause significant economic losses throughout the world. Vaccines are available, but they are based on one PRRSV strain, and there is evidence that PRRSV strains vary at the antigenic and genetic levels. In addition, since the virus was identified in Europe and in the United States, new disease phenotypes have continued to emerge.